ES2904317T3 - Dinucleótidos cíclicos como agentes anticancerosos - Google Patents
Dinucleótidos cíclicos como agentes anticancerosos Download PDFInfo
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- ES2904317T3 ES2904317T3 ES18766543T ES18766543T ES2904317T3 ES 2904317 T3 ES2904317 T3 ES 2904317T3 ES 18766543 T ES18766543 T ES 18766543T ES 18766543 T ES18766543 T ES 18766543T ES 2904317 T3 ES2904317 T3 ES 2904317T3
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- nra1ra1
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- acceptable salt
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- C07H21/02—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with ribosyl as saccharide radical
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| US11660311B2 (en) | 2017-10-10 | 2023-05-30 | Bristol-Myers Squibb Company | Cyclic dinucleotides as anticancer agents |
| PH12020550585A1 (en) | 2017-11-10 | 2021-04-19 | Takeda Pharmaceuticals Co | Sting modulator compounds, and methods of making and using |
| WO2019125974A1 (en) * | 2017-12-20 | 2019-06-27 | Merck Sharp & Dohme Corp. | Cyclic di-nucleotide compounds as sting agonists |
| JP7037667B2 (ja) | 2017-12-20 | 2022-03-16 | インスティチュート オブ オーガニック ケミストリー アンド バイオケミストリー エーエスシーアール，ヴイ．ヴイ．アイ． | Ｓｔｉｎｇアダプタータンパク質を活性化するホスホン酸結合を有する３’３’環状ジヌクレオチド |
| US11203610B2 (en) | 2017-12-20 | 2021-12-21 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 2′3′ cyclic dinucleotides with phosphonate bond activating the sting adaptor protein |
| US10519187B2 (en) | 2018-02-13 | 2019-12-31 | Bristol-Myers Squibb Company | Cyclic dinucleotides as anticancer agents |
| JP7250808B2 (ja) * | 2018-03-08 | 2023-04-03 | ブリストル－マイヤーズ スクイブ カンパニー | 抗がん剤としての環状ジヌクレオチド |
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| US12251394B2 (en) | 2018-06-01 | 2025-03-18 | Eisai R&D Management Co., Ltd. | Methods for the treatment of bladder cancer |
| US11110106B2 (en) | 2018-10-29 | 2021-09-07 | Venenum Biodesign, LLC | Sting agonists for treating bladder cancer and solid tumors |
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| WO2021068866A1 (en) | 2019-10-10 | 2021-04-15 | Beigene, Ltd. | Heterocyclic compounds as sting modulators |
| US20230141284A1 (en) | 2020-04-10 | 2023-05-11 | Ono Pharmaceutical Co., Ltd. | Cancer therapeutic method |
| CN115667274B (zh) | 2020-05-28 | 2025-04-29 | 百济神州有限公司 | 作为sting调节剂的杂环化合物 |
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Family Cites Families (47)
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| CN102918061B (zh) | 2010-03-05 | 2016-06-08 | 霍夫曼-拉罗奇有限公司 | 针对人csf-1r的抗体及其用途 |
| EP3943154A1 (en) | 2010-05-04 | 2022-01-26 | Five Prime Therapeutics, Inc. | Antibodies that bind csf1r |
| NZ729044A (en) | 2010-09-09 | 2020-07-31 | Pfizer | 4-1bb binding molecules |
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| CA2833636A1 (en) | 2011-04-20 | 2012-10-26 | Amplimmune, Inc. | Antibodies and other molecules that bind b7-h1 and pd-1 |
| MX356337B (es) | 2011-12-15 | 2018-05-23 | Hoffmann La Roche | Anticuerpos contra csf-1r humano y sus usos. |
| MX2014008961A (es) | 2012-02-06 | 2014-10-14 | Genentech Inc | Composiciones y metodos para utilizar inhibidores de csf1r. |
| AR090263A1 (es) | 2012-03-08 | 2014-10-29 | Hoffmann La Roche | Terapia combinada de anticuerpos contra el csf-1r humano y las utilizaciones de la misma |
| KR20150018533A (ko) | 2012-05-11 | 2015-02-23 | 파이브 프라임 테라퓨틱스, 인크. | 콜로니 자극 인자 1 수용체(csf1r)에 결속하는 항체들에 의한 질병 상태의 치료 방법 |
| US9175082B2 (en) | 2012-05-31 | 2015-11-03 | Sorrento Therapeutics, Inc. | Antigen binding proteins that bind PD-L1 |
| AR091649A1 (es) | 2012-07-02 | 2015-02-18 | Bristol Myers Squibb Co | Optimizacion de anticuerpos que se fijan al gen de activacion de linfocitos 3 (lag-3) y sus usos |
| CN107759690A (zh) | 2012-08-31 | 2018-03-06 | 戊瑞治疗有限公司 | 用结合群落刺激因子1受体(csf1r)的抗体治疗病状的方法 |
| JP2016524593A (ja) * | 2013-04-29 | 2016-08-18 | メモリアル スローン−ケタリング キャンサー センター | セカンドメッセンジャーのシグナル伝達を変えるための組成物及び方法 |
| RS61400B1 (sr) | 2013-05-02 | 2021-02-26 | Anaptysbio Inc | Antitela usmerena protiv programirane smrti-1 (pd-1) |
| CU24377B1 (es) * | 2013-05-18 | 2018-12-05 | Aduro Biotech Inc | Dinucléotidos de purina cíclicos y composiciones de los mismos útiles para inducir la producción de interferón de tipo i dependientes de sting |
| EP2996472B1 (en) * | 2013-05-18 | 2019-03-27 | Aduro Biotech, Inc. | Compositions and methods for inhibiting "stimulator of interferon gene" dependent signalling |
| CA3175360C (en) | 2013-05-31 | 2024-05-28 | Sorrento Therapeutics, Inc. | Antigen binding proteins that bind pd-1 |
| SMT202300039T1 (it) | 2013-09-13 | 2023-03-17 | Beigene Switzerland Gmbh | Anticorpi anti-pd1 e loro uso come terapia e per diagnostica |
| JP2016538344A (ja) * | 2013-11-19 | 2016-12-08 | ザ・ユニバーシティ・オブ・シカゴＴｈｅ Ｕｎｉｖｅｒｓｉｔｙ Ｏｆ Ｃｈｉｃａｇｏ | 癌処置としてのｓｔｉｎｇアゴニストの使用 |
| CR20160319A (es) | 2013-12-12 | 2016-11-08 | Jiangsu Hengrui Medicine Co | Anticuerpo pd-1, fragmento de union al antigeno de este y uso médico de este |
| TWI681969B (zh) | 2014-01-23 | 2020-01-11 | 美商再生元醫藥公司 | 針對ｐｄ-１的人類抗體 |
| UA122479C2 (uk) | 2014-01-24 | 2020-11-25 | Дана-Фарбер Кенсер Інстітьют, Інк. | Виділена молекула антитіла, яка зв’язується з людським білком програмованої смерті-1 (pd-1) |
| GB201501462D0 (en) * | 2015-01-29 | 2015-03-18 | Glaxosmithkline Ip Dev Ltd | Novel compounds |
| TWI706958B (zh) * | 2015-03-10 | 2020-10-11 | 美商艾杜諾生物科技公司 | 活化「干擾素基因刺激因子」依賴性訊息傳導之組合物及方法 |
| MA42971A (fr) | 2015-03-13 | 2018-08-15 | Cytomx Therapeutics Inc | Anticorps anti-pdl1, anticorps anti-pld1 activables, et leurs procédés d'utilisation |
| CN108137641B (zh) * | 2015-08-13 | 2022-04-01 | 默沙东公司 | 作为sting激动剂的环状双核苷酸化合物 |
| KR20180066241A (ko) * | 2015-10-28 | 2018-06-18 | 아두로 바이오테크, 인코포레이티드 | “인터페론 유전자의 자극제”-의존성 신호전달을 활성화시키기 위한 조성물 및 방법 |
| JP6411676B2 (ja) * | 2015-12-03 | 2018-10-24 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドＧｌａｘｏｓｍｉｔｈｋｌｉｎｅ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ Ｄｅｖｅｌｏｐｍｅｎｔ Ｌｉｍｉｔｅｄ | Ｓｔｉｎｇの調節因子としての環状プリンジヌクレオチド |
| DE212016000029U1 (de) * | 2015-12-07 | 2017-07-30 | Opi Vi - Ip Holdco Llc | Zusammensetzungen von Antikörperkonstrukt-Agonist-Konjugaten |
| US20180369268A1 (en) * | 2015-12-16 | 2018-12-27 | Aduro Biotech, Inc. | Methods for identifying inhibitors of "stimulator of interferon gene"- dependent interferon production |
| WO2017123657A1 (en) | 2016-01-11 | 2017-07-20 | Gary Glick | Cyclic dinucleotides for treating conditions associated with sting activity such as cancer |
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2018
- 2018-08-30 JP JP2020512379A patent/JP7208225B2/ja active Active
- 2018-08-30 KR KR1020207008751A patent/KR102674630B1/ko active Active
- 2018-08-30 ES ES18766543T patent/ES2904317T3/es active Active
- 2018-08-30 EP EP18766543.5A patent/EP3676279B1/en active Active
- 2018-08-30 US US16/642,424 patent/US10953032B2/en active Active
- 2018-08-30 WO PCT/US2018/048666 patent/WO2019046500A1/en not_active Ceased
- 2018-08-30 CN CN201880055913.XA patent/CN111051328B/zh active Active
Also Published As
| Publication number | Publication date |
|---|---|
| JP2020532529A (ja) | 2020-11-12 |
| KR20200042938A (ko) | 2020-04-24 |
| WO2019046500A1 (en) | 2019-03-07 |
| CN111051328B (zh) | 2023-11-03 |
| JP7208225B2 (ja) | 2023-01-18 |
| CN111051328A (zh) | 2020-04-21 |
| US10953032B2 (en) | 2021-03-23 |
| EP3676279B1 (en) | 2021-12-01 |
| KR102674630B1 (ko) | 2024-06-11 |
| US20200253997A1 (en) | 2020-08-13 |
| EP3676279A1 (en) | 2020-07-08 |
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